Concurrent MEK targeted therapy prevents MAPK pathway reactivation during BRAFV600E targeted inhibition in a novel syngeneic murine glioma model.

Inhibitors of BRAFV600E kinase are currently under investigations in preclinical and clinical studies involving BRAFV600E glioma. Studies demonstrated clinical response to such individualized therapy in the majority of patients whereas in some patients tumors continue to grow despite treatment. To study resistance mechanisms, which include feedback activation of mitogen-activated protein kinase (MAPK) signaling in melanoma, we developed a luciferase-modified cell line (2341luc) from a BrafV600E mutant and Cdkn2a- deficient murine high-grade glioma, and analyzed its molecular responses to BRAFV600E- and MAPK kinase (MEK)-targeted inhibition. Immunocompetent, syngeneic FVB/N mice with intracranial grafts of 2341luc were tested for effects of BRAFV600E and MEK inhibitor treatments, with bioluminescence imaging up to 14-days after start of treatment and survival analysis as primary indicators of inhibitor activity. Intracranial injected tumor cells consistently generated high-grade glioma-like tumors in syngeneic mice. Intraperitoneal daily delivery of BRAFV600E inhibitor dabrafenib only transiently suppressed MAPK signaling, and rather increased Akt signaling and failed to extend survival for mice with intracranial 2341luc tumor. MEK inhibitor trametinib delivered by oral gavage daily suppressed MAPK pathway more effectively and had a more durable anti-growth effect than dabrafenib as well as a significant survival benefit. Compared with either agent alone, combined BRAFV600E and MEK inhibitor treatment was more effective in reducing tumor growth and extending animal subject survival, as corresponding to sustained MAPK pathway inhibition. Results derived from the 2341luc engraftment model application have clinical implications for the management of BRAFV600E glioma

Enhancing Social Diversity and Communication in an Assisted Living Facility for Older Adults: A Community Health Nursing Project

Improving the health of specific populations requires community partnerships, collaboration, and an in-depth understanding of the diverse health status and health care needs of the population.  The purpose of this paper is to describe a community health project that the authors, in conjunction with the staff and residents, implemented at an assisted living facility for older adults who needed assistance with activities of daily living but who were otherwise fairly independent. The LODGE (pseudonym) community is located in a large urban centre in Western Canada.  The focus of this three and half month project was to gain information about this community in order to help optimize the function and independence of its members. The guiding frameworks included the nursing process, the Community as a Partner model and the Population Health model. The community assessment included a windshield survey, a general survey of 142 residents living in the facility (74% response rate), key informant interviews, literature review, and several brainstorming sessions with staff and residents.  The focus of data analysis was on the salient areas of strength and areas that needed improvement. The major finding regarding how to best optimize the function and independence of the residents included interventions related to (a) obtaining a more specific in-depth interview with residents who are inactive in both a physical and social sense in order to obtain more specific information about the activities and interests they valued in the past, and which ones they could still participate in if specific types of resources were provided , (b) enhancing relational communication and (c) increasing accessibility to information regarding the eligibility and benefits of the government funded Home Care services.  Interventions were viewed positively by members of the community. Recommendations are provided for expansion and sustainability of future community interventions. &nbsp

The Dark Matter Distributions in Low-mass Disk Galaxies. II. The Inner Density Profiles

Dark-matter-only simulations predict that dark matter halos have steep, cuspy inner density profiles, while observations of dwarf galaxies find a range of inner slopes that are often much shallower. There is debate whether this discrepancy can be explained by baryonic feedback or if it may require modified dark matter models. In Paper I of this series, we obtained high-resolution integral field Hα observations for 26 dwarf galaxies with M* = 10^(8.1)−10^(9.7) M_⊙. We derived rotation curves from our observations, which we use here to construct mass models. We model the total mass distribution as the sum of a generalized Navarro–Frenk–White (NFW) dark matter halo and the stellar and gaseous components. Our analysis of the slope of the dark matter density profile focuses on the inner 300–800 pc, chosen based on the resolution of our data and the region resolved by modern hydrodynamical simulations. The inner slope measured using ionized and molecular gas tracers is consistent, and it is additionally robust to the choice of stellar mass-to-light ratio. We find a range of dark matter profiles, including both cored and cuspy slopes, with an average of ρ}_(DM ~ r^(-0.74 ± 0.07), shallower than the NFW profile, but steeper than those typically observed for lower-mass galaxies with M* ~ 10^(7.5) M_⊙. Simulations that reproduce the observed slopes in those lower-mass galaxies also produce slopes that are too shallow for galaxies in our mass range. We therefore conclude that supernova feedback models do not yet provide a fully satisfactory explanation for the observed trend in dark matter slopes

Математическое моделирование системы отслеживания шва в сварке электронным пучком

В ходе исследований разработана математическая модель системы отслеживания шва в сварке электронным пучком. Экспериментально доказана эффективность применения данной модели к любой электронно-сварочной установке. Для простейшего детектора излучения (пластины-детектора) без использования физических фильтров были получены электронные изображения сварных швов, отличающиеся высокой четкостью. Эмпирически доказана независимость сканирования от механических характеристик электронно-сварочной установки. Доказано, что отсутствие источников электронов с необходимой мощностью пучка не является препятствием для получения достаточного качества измерений.In the course of research, a mathematical model of the tracking system of a weld in electron beam welding was developed. The effectiveness of applying this model to any electronic welding installation has been experimentally proven. For the simplest radiation detector (detector plate) without the use of physical filters, electronic images of welds, which are distinguished by high definition, were obtained. Empirically proven independence of the scan from the mechanical characteristics of the electronic welding installation. It is proved that the absence of electron sources with the necessary beam power is not an obstacle to obtaining a sufficient measurement quality

Applying generalizability theory to examine assessments of subjective cognitive complaints: whose reports should we rely on - participant versus informant?

OBJECTIVES: This study aimed to apply the generalizability theory (G-theory) to investigate dynamic and enduring patterns of subjective cognitive complaints (SCC), and reliability of two widely used SCC assessment tools. DESIGN: G-theory was applied to assessment scales using longitudinal measurement design with five assessments spanning 10 years of follow-up. SETTING: Community-dwelling older adults aged 70-90 years and their informants, living in Sydney, Australia, participated in the longitudinal Sydney Memory and Ageing Study. PARTICIPANTS: The sample included 232 participants aged 70 years and older, and 232 associated informants. Participants were predominantly White Europeans (97.8%). The sample of informants included 76 males (32.8%), 153 females (65.9%), and their age ranged from 27 to 86 years, with a mean age of 61.3 years (SD = 14.38). MEASUREMENTS: The Memory Complaint Questionnaire (MAC-Q) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). RESULTS: The IQCODE demonstrated strong reliability in measuring enduring patterns of SCC with G = 0.86. Marginally acceptable reliability of the 6-item MAC-Q (G = 0.77-0.80) was optimized by removing one item resulting in G = 0.80-0.81. Most items of both assessments were measuring enduring SCC with exception of one dynamic MAC-Q item. The IQCODE significantly predicted global cognition scores and risk of dementia incident across all occasions, while MAC-Q scores were only significant predictors on some occasions. CONCLUSIONS: While both informants' (IQCODE) and self-reported (MAC-Q) SCC scores were generalizable across sample population and occasions, self-reported (MAC-Q) scores may be less accurate in predicting cognitive ability and diagnosis of each individual

Accidental benzene release risk assessment in an urban area using an atmospheric dispersion model

This study applied the American Meteorological Society and Environmental Protection Agency Regulatory Model (AERMOD) to assess the risk caused by an accidental release and dispersion of the toxic chemical benzene in the vicinity of a highly populated urban area. The modeling domain encompasses the Korean megacity of Ulsan, which includes two national industrial complexes and is characterized by a complex coastal terrain. Multiple AERMOD simulations were conducted for an assumed emission scenario using background wind data from August between 2009 and 2013. The series of experiments produced the spatial accident probability patterns for different concentration levels during daytime and nighttime scenarios based on the corresponding dominant wind patterns. This study further quantifies the potential accident risk based on the number of affected individuals by combining the accident probability with the indoor and outdoor population estimates. The chemical gas dispersion characteristics depend on various local meteorological conditions, such as the land-sea breeze direction, which alternates between daytime and nighttime, and the atmospheric stability. The results reveal that benzene dispersion affects a much larger area during the nighttime owing to the presence of a nocturnal stable boundary layer with significant temperature stratification. The affected area is smaller during the daytime owing to decreased stability and enhanced vertical mixing in the boundary layer. The results include a high degree of uncertainty during the nighttime owing to weak wind speeds and the lack of a prevailing wind direction, which impact the vulnerable area. However, vulnerable areas are more effectively identified during the daytime, when more consistent meteorological conditions exist. However, the potential risk becomes much lower during the nighttime owing to a substantial reduction of the outdoor population.ope